27.1: Classification of Amino Acids. Chapter 27: Amino Acids, Peptides, and Proteins. monomer unit:

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Transcript of 27.1: Classification of Amino Acids. Chapter 27: Amino Acids, Peptides, and Proteins. monomer unit:

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    307

    Chapter 27: Amino Acids, Peptides, and Proteins. monomer unit: α-amino acids

    Biopolymer: the monomeric amino acids are linked through an amide bond (the carboxylic acids of one AA with the α-amino group of a second)

    peptide (< 50 amino acids) protein (> 50 amino acids)

    R CO2H

    NH2H

    !- Amino Acid

    R = sidechain

    R1

    H3N CO2

    R2

    H3N CO2

    + - H2O R1

    H3N

    H N

    O

    CO2

    R2

    C-terminus

    N-terminus

    Peptide or protein (polypeptide)

    N H

    O

    R3

    H N

    O

    R2

    N H

    O

    R1

    H N

    N H

    O

    R7

    H N

    O

    R6

    N H

    O

    R5

    R4 H N

    O

    308

    27.1: Classification of Amino Acids. AA’s are classified according to the location of the amino group.

    There are 20 genetically encoded α-amino acids found in peptides and proteins

    19 are primary amines, 1 (proline) is a secondary amine 19 are “chiral”, 1 (glycine) is achiral; the natural configuration of the α-carbon is L.

    !-amino acid (2-amino carboxylic acid)

    C CO2HH2N

    H

    H

    C CO2HC

    H

    H

    H2N

    H

    H

    C CC

    H

    H

    H2N

    H

    H

    CO2H

    H

    H

    "-amino acid (3-amino carboxylic acid)

    #-amino acid (4-amino carboxylic acid)

    CO2H

    CH3

    H2N H

    CO2H

    R

    H2N H

    L-alanine

    CHO

    HO H

    H OH

    CH2OH

    CHO

    H OH

    HO H

    CH2OH

    L-erythroseD-erythrose

    CO2H

    H2N H

    H OH

    CH3

    CO2H

    H2N H

    H3C H

    CH2CH3

    L-theronine (2S,3R)

    L-isoleucine (2S,3S)

    CHO

    CH2OH

    H OH

    D-glyceraldehyde

    CHO

    CH2OH

    HO H

    L-glyceraldehyde

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    α-Amino acids are classified by the properties of their sidechains. Nonpolar:

    (S)-(+)-Valine (Val, V)

    (S)-(–)-Tryptophan (Trp, W)(S)-(–)-Proline (Pro, P) (S)-(–)-Phenylalanine (Phe, F)

    COO–

    NH3

    H

    N

    H

    COO–

    NH3

    COO–

    NH3

    COO–

    NH3

    NH3

    COO–

    COO–

    (2S,3S)-(+)-Isoleucine (Ile, I)

    (S)-(+)-Alanine (Ala, A)

    (S)-(–)-Leucine (Leu, L)

    Glycine (Gly, G)

    NH3

    COO–

    COO–

    NH3N H

    NH3

    COO–S

    (S)-(–)-Methionine (Met, M)

    Polar but non-ionizable:

    (S)-(+)-Glutamine (Gln, Q)

    H2N

    O

    NH3

    COO–

    (S)-(–)-Tyrosine (Tyr, Y)(2S,3R)-(–)-Threonine (Thr, T)(S)-(–)-Serine (Ser, S)

    COO–

    NH3

    COO–

    NH3

    COO–

    NH3 NH3

    COO–

    NH3

    COO–

    O

    H2NHS

    HO

    OH

    HO

    (R)-(–)-Cysteine (Cys, C) (S)-(–)-Asparagine (Asn, N)

    pKa ~ 13 pKa ~ 13

    pKa ~ 8.2

    pKa ~ 10.1

    310

    Acidic:

    Basic:

    (S)-(–)-Histidine (His, H)

    NH3

    COO– COO–

    NH3 NH3

    COO– N

    H

    N N

    H

    H

    (S)-(+)-Lysine (Lys, K) (S)-(+)-Arginine (Arg, R)

    pKa ~ 10.5 pKa ~ 6.0 pKa ~ 12.5

    H2N

    N H H

    H3N

    -O

    O NH3

    COO–

    (S)-(+)-Aspartic Acid (Asp, D)

    COO–

    NH3

    O

    -O

    (S)-(+)-Glutamic Acid (Glu, E)

    pKa ~ 3.6 pKa ~ 4.2

    27.2: Stereochemistry of Amino Acids: The natural configuration of the α-carbon is L. D-Amino acids are found in the cell walls of bacteria. The D-amino acids are not genetically encoded, but derived from the epimerization of L-isomers

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    27.3: Acid-Base Behavior of Amino Acids. Amino acids exist as a zwitterion: a dipolar ion having both a formal positive and formal negative charge (overall charge neutral).

    CO2H

    R

    H

    H2N CO2

    R

    H

    H3N _+

    Amino acids are amphoteric: they can react as either an acid or a base. Ammonium ion acts as an acid, the carboxylate as a base.

    Isoelectric point (pI): The pH at which the amino acid exists largely in a neutral, zwitterionic form (influenced by the nature of the sidechain)

    pKa ~ 5 pKa ~ 9

    CO2

    R

    H

    H3N _+CO2H

    R

    H

    H3N +

    CO2

    R

    H

    H2N HO

    _

    pKa2 low pH high pH

    _H3O +

    pKa1

    Table 27.2 (p. 1115) & 27.2 (p. 1116)

    312

    pI = pKax + pKay

    2

    CO2

    CH3

    H

    H3NCO2H

    CH3

    H

    H3N

    low pH

    CO2

    CH3

    H

    H2N + +

    high pH

    pKa1 (2.3)

    pKa2 (9.7)

    CO2H

    CH2

    H

    H3N

    CO2H

    pKa3 (3.6)

    CO2

    H

    H3N

    CH2

    CO2H

    CO2

    H

    H3N

    CH2

    CO2

    pKa2 (9.6)

    pKa1 (1.9)

    CO2

    H

    H2N

    CH2

    CO2

    low pH high pH

    CO2H

    (CH2)4

    H

    H3N

    NH3

    pKa2 (9.0)

    CO2

    H

    H3N

    (CH2)4

    NH3

    CO2

    H

    H2N

    (CH2)4

    NH3

    pKa3 (10.5)

    pKa1 (2.2)

    CO2

    H

    H2N

    (CH2)4

    NH2

    low pH high pH

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    Electrophoresis: separation of polar compounds based on their mobility through a solid support. The separation is based on charge (pI) or molecular mass.

    + _

    _ _ _ _ + + + +

    + _

    314

    Strecker Synthesis: recall reductive amination

    C CO2HR

    O NH3

    C CO2HR

    NH2

    H

    NaB(CN)H3

    R C CO2H

    NH2

    H

    C HR

    O NH3

    C HR

    NH2 NaC!N

    N!C:

    R C C!N

    NH2

    H

    H3O +

    -or- NaOH, H2O

    R C CO2H

    NH2

    H

    Amidomalonate Synthesis: recall the malonic acid synthesis

    H CO2Et C

    CO2EtHN EtO Na

    RCH2X

    H3O

    - CO2 RCH2 CO2H C

    HH2N

    O

    RCH2 CO2Et C

    CO2EtHN

    O

    R-CH2-CO2H R C CO2H

    Br

    R C CO2H

    NH2 Br2, PBr3 NH3

    H H

    27.5: Synthesis of Amino Acids:

    Ch. 19.16

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    R CO2

    H3N H H3C O CH3

    O O

    base R CO2H

    HN H

    O

    H3C

    HOCH2CH3

    H+R CO2CH2CH3

    H2N H

    27.6: Some Biochemical Reactions of Amino Acids. Many enzymes involved in amino acid biosynthesis, metabolism and catabolism are pyridoxal phosphate (vitamin B6) dependent (please read)

    NH3

    R CO2 -

    H

    L-amino acid

    NH3

    R H CO2

    -

    D-amino acid

    racemase, epimerase

    H3N

    R H

    H

    decarboxylase

    O

    R CO2 -

    transaminase

    N

    2-O3PO OH

    O H

    pyridoxal phosphate (PLP)

    +

    N H

    PO

    N

    OH

    CO2 -R

    27.5: Reactions of Amino Acids. Amino acids will undergo reactions characteristic of the amino (amide formation) and carboxylic acid (ester formation) groups.

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    27.7: Peptides. Proteins and peptides are polymers made up of amino acid units (residues) that are linked together through the formation of amide bonds (peptide bonds) from the amino group of one residue and the carboxylate of a second residue

    By convention, peptide sequences are written left to right from the N-terminus to the C-terminus

    H2N CO2H

    Alanine

    H2N CO2H

    HO

    Serine

    + - H2O H2N

    H N

    O

    CO2H

    OH

    Ala - Ser (A - S)- H2O

    H2N

    H N

    O

    CO2H

    HO

    Ser - Ala (S - A)

    C-terminus

    N-terminus

    C-terminus

    N-terminus

    N H

    O

    R3

    H N

    O

    R2

    N H

    O

    R1

    H N

    N H

    O

    R7

    H N

    O

    R6

    N H

    O

    R5

    R4 H N

    O

    backbone

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    The amide (peptide) bond has C=N double bond character due to resonance resulting in a planar geometry

    restricts rotations resistant to hydrolysis

    R1

    H N

    N

    O R2 H N

    O

    amide bond

    R1

    H N

    N

    O R2 H N

    O

    _

    +

    H H

    The N-H bond of one amide linkage can form a hydrogen bond with the C=O of another.

    N

    N

    O

    H

    R

    O

    H

    N

    N

    O

    H

    R

    O

    H

    N

    N

    O

    H

    R

    O

    H

    N-O distance 2.85 - 3.20 Å optimal N-H-O angle is 180 °

    Disulfide bonds: the thiol groups of cysteine can be oxidized to form disulfides (Cys-S-S-Cys)

    SH HO2C

    NH2 2

    1/2 O2 H2O

    S HO2C

    NH2

    S CO2H

    NH2H2

    318

    N H

    O

    R2

    H N

    O

    R1

    N H

    H N

    O

    R5

    N H

    O

    R4

    H N

    O

    N H

    O H N

    O

    R6

    N H

    H N